The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade

Objective: Circulating levels of IGF-I and IGFBP-3 are low in cirrhosis and are related to liver dysfunction. Metabolic disturbances include malnutrition with altered body composition and osteopenia. Since the effects of IGF-I may be associated to changes in body composition and bone mineral content (BMC) in cirrhotic patients, we investigated the relations between changes in the IGF-system and body composition and the effects of long-term alpha- and beta-blockade. Design: The study was designed as a combined cross-sectional and prospective randomised controlled study of 62 patients with cirrhosis. Twenty-three of these patients were randomised to treatment with beta- or combined alpha/beta-blocker for 3 months. Haemodynamics, body composition, and systemic and hepatic IGF-I and IGFBP-3 levels were determined in all patients. In the subgroup changes in body composition and IGF-I/IGFBP-3 levels after 3 months of beta- or combined alpha/beta-blockade were additionally examined. Results: Both the hepatic and the systemic IGF systems were suppressed and correlated with liver dysfunction and anthropometrics (p<0.05-0.001). Multivariate analyses revealed that changes in the IGF-system were determined by metabolic liver dysfunction as well as anthropometrics. In the follow-up study, hepatic venous IGF-I (p = 0.05) and IGFBP-3 (p = 0.02) increased after 3 months only in the group who received beta-blocker. In both groups, fat body mass increased significantly after 3 months (p = 0.05-0.001). Conclusions: In cirrhosis, the IGF-system is associated with both anthropometrics and synthetic capacity of the liver. Changes in IGF-I relate to changes in anthropometrics and there seems to be a differential effect depending on the type of adrenoreceptor blockade. Future longitudinal studies are needed to unravel these mechanisms in cirrhosis. (C) 2012 Elsevier Ltd. All rights reserved.